title: IFN-gamma reduction by tricyclic antidepressants.
abstract: OBJECTIVE
  A growing body of data indicates that an activation of proinflammatory cytokines such as interferon-gamma (IFN-gamma) is involved in the pathophysiology of depression and that the suppression of pro-inflammatory cytokine production by antidepressants may lead to an improvement of depressive symptoms. However, the influence of the serotonin and noradrenalin reuptake inhibitor (SNRI) venlafaxine and its metabolite O-desmethylvenlafaxine on the stimulated blood cell secretion of IFN-gamma has not been studied so far.
  
  
  METHODS
  We measured IFN-gamma levels in the stimulated blood of healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was either supplemented with antidepressants or not.
  
  
  RESULTS
  Mean IFN-gamma concentrations differed between blood with and without antidepressant supplements (p = 0.026). Planned contrasts revealed that compared to non-supplemented blood, four of the blood samples supplemented with the tricyclic antidepressants (TCAs) reduced IFN-gamma levels: amitriptyline (adjusted p-value (p = 0.004), nortriptyline (p = 0.037), imipramine (p = 0.021), and desipramine (p = 0.048). There was no significant difference between the control condition and the venlafaxine or O-desmethylvenlafaxine condition.
  
  
  CONCLUSIONS
  TCAs might, among other mechanisms, act as antidepressants by suppressing the production of pro-inflammatory cytokines, whereas no significant effect of venlafaxine and O-desmethylvenlafaxine on IFN-gamma secretion could be demonstrated.
authors.affiliation: Aachen University, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Himmerich
authors.forename: Stephany
authors.initials: S
authors.lastname: Fulda
authors.forename: Abigail J
authors.initials: AJ
authors.lastname: Sheldrick
authors.forename: Birgit
authors.initials: B
authors.lastname: Plümäkers
authors.forename: Lothar
authors.initials: L
authors.lastname: Rink
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D003866:Depressive Disorder / Q000276:immunology*; D003891:Desipramine / Q000494:pharmacology; D000069468:Desvenlafaxine Succinate; D005260:Female; D006801:Humans; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D009661:Nortriptyline / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D016207:Cytokines; D000639:Amitriptyline; D000069470:Venlafaxine Hydrochloride; D007371:Interferon-gamma; D009661:Nortriptyline; D007099:Imipramine; D003891:Desipramine; D000069468:Desvenlafaxine Succinate